Ren Zhang, PhD

Education

The University of Texas MD Anderson Cancer Center, PhD

Research Focus

Patients with metabolic syndrome are at high risk for developing atherosclerotic cardiovascular diseases and diabetes, a major public health burden. The Zhang lab recently identified two novel lipid metabolism regulators, (1) lipasin and (2) MNADK, both being encoded by previously uncharacterized genes. The lab currently focuses on the characterizations of functional roles of lipasin and MNADK in mediating lipid metabolism and glucose homeostasis.

(1)Lipasin/Angplt8, a novel lipid metabolism regulator.In addition to LDL-cholesterol, elevated plasma triglycerides are increasingly recognized as an independent risk factor for cardiovascular diseases. The Zhang lab recently identified a novel triglyceride metabolism regulator, encoded by a previously uncharacterized gene, Gm6484, which was then named lipasin, also known as RIFL and Angptl8. Serum triglyceride levels are decreased or increased in lipasin-deficient or -overexpressing mice, respectively. Lipasin expression, specific to the liver and adipose tissues, is dramatically induced by food intake and reduced by fasting. In humans, plasma levels of lipasin—which is secreted by the liver—are elevated in both type 1 and type 2 diabetes, and its sequence variations are associated with lipid profiles by multiple genome-wide association studies. Lipasin is a novel but atypical member of the ANGPTL

(2)MNADK represents a novel pathway in generating mitochondrial NADP. Nicotinamide adenine dinucleotide phosphate (NADP) plays essential roles in lipid metabolism. NADP is required by mitochondria for fatty acid β-oxidation to generate energy, and for regenerating oxidative defense systems to neutralize reactive oxygen species. The NAD kinase (NADK) is the sole NADP biosynthetic enzyme, but human mitochondrial NAD kinase remained unidentified for many years. The Zhang lab recently discovered that the uncharacterized human gene C5ORF33 encodes the long-sought mitochondrion-localized NADK, referred to as MNADK, also later known as NADK2. MNADK is a mitochondrial NADK that is enriched and nutritionally-regulated in mouse liver, and a MNADK-deficient patient exhibits symptoms characteristic of mitochondrial disease. Mnadk knockout mice phenocopy the MNADK-deficient patient by having elevated plasma lysine and C10:2 carnitine. The identification of MNADK provides a key clue to the mechanisms for mitochondrial NADP(H) production and the maintenance of its redox balance in mammalian cells (Fig. 2).